The hypothesis to be tested in this proposal is that modifying the cell number of a developing organ can have consequences on the organ's function during adult life. We will focus our attention on the developing heart. This choice is based on the ability of cardiac cell number to be regulated pathophysiologically during development. A major hypothesis of this Program Project Grant is that intrauterine stresses can modify the program governing cell growth in adult life. For the heart, this is often associated with the stimulation of cardiomyocyte hyperplasia and an alteration in adult heart function. A corollary of this hypothesis is that alterations in cell number can affect cardiac function. This will be tested using genetically modified animal models of cardiac function. Initial studies will determine the program of cell growth in the heart (Specific Aim 1). Subsequent Aims will test the hypothesis that modifying ERK function will have consequences on cell growth during cardiac development, and on cardiovascular function in the adult. In Specific Aim 1 we will determine the critical period when ERK activity and proliferative signals pathways are maximal during organogenesis of the heart. In Specific Aim 2 we will introduce these modifiers of ERK signaling into whole animal models in such a way that their expression limited to the cardiomyocyte. In Specific Aim 3 we will determine whether these modifiers have pathophysiological consequences of the altered developmental processes on heart function during he lifetime of the animal.